Medicinal compositions and method for relieving cough



United States Patent e 3,156,614 a MEDICINAL CQMPOSITIONS AND METHOD FUR REHEVING CQUGH Donald R. MacDonneli, Raduor, Pa, assignor to $mith Kline & French Laboratories, Phiiadeiphia, Pa, a cerporation of Pennsyivania f. No Drawing. Fiied Aug. 23, 1962, Ser. No. 218,867 9 Claims. (Cl. 167-54) The present invention relates to an improved medicinal composition and a prompt and convenient method for the treatment of conditions of the tissues of the upper respiratory tract such as the relief from cough and nasal congestion. More particularly the present invention relates to an improved method for obtaining relief from cough- Up to the present time cough relief has been achieved through the use of oral preparations such as syrups, cough drops, tablets, capsules and throat sprays. These prior art cough remedies must be absorbed from the gastrointestinal tract before they can take effect and therefore a prompt relief is notachieved. These prior art cough remedies are also inconvenient to take. at times. For example, if a coughing seizure occurs during thenight the patient must go through the inconvenience of leaving his bed to obtain water in order to wash down his cough tablet or capsule. Further, when coughing'seizures occur in public places such as the theatre they prove very embarrassing when prompt relief is not available. If a patient is taking a cough syrup he must carry a cumbersome and sometimes leaking container if it is necessary to take the medication during employment hours. Further, if the patient were suffering with nasal congestion along with his cough he finds it necessary to take several medicaments to get relief, i.e., nasal decongestants plus his cough medicine.

It is an object of this invention to overcome the difiiculties encountered by the prior art cough compositions and provide for an improved composition and method for a prompt and convenient relief of cough associated with upper respiratory infections which is both safe and effective.

It is a further object of this invention to provide an improved medicinal composition and a method for obtaining a prompt and convenient relief for cough while concurrently relieving nasal congestion which is both safe and effective.

The medicinal compositions and method of this invention are in inhaler form and comprises volatile ingredients which are administered in vapor form directly to the congested, irritated membrances of the nasopharyngeal tract that initiate the cough reflex. Unlike cold tablets or capsules, the compositions as administered by this invention do not have to be absorbed by the gastrointestinal tract to take effect and therefore result in prompt relief. The vapors as administered by the present invention can also reach areas of the nose, pharynx, larynx and upper bronchial tract inaccessible to drops or sprays.

The compositions of this invention being in inhaler form also allow' for the administration of the effective medicament in a pharmaceutical form both convenient for administration as well as pleasant for patient acceptance. The inhaler can be carried in the pocket and can be concealed in the hand and used inconspicuously whenever and wherever needed. It can be placed on a night table and cough seizures during the night can be taken care of without any fuss or bother. Further, because of the distinct inhaler package, there is no danger of a sleepy individual taking the wrong medication during the night.

The method of relieving cough in accordance with this invention comprises administering intranasally a vapor dosage unit of from about 0.25 mg. to about 1.5 mg. of

2-amino-6-methylheptane to the irritated mucous menibrane of the upper respiratory tract. The vapor dosage unit may be advantageously administered from one to eight times daily. Preferably the daily dose will be from about 0.25 mg. to about 12.0 mg. of active ingredients. The administration of a vapor dosage unit is accomplished by inserting the inhaler into each nostril and taking two 'inhalations, i.e.,,a total of four inhalations, two in each nostril is recognized as a vapor dosage unit.

A further advantageous method of relieving cough while concurrently relieving nasal congestion comprises administeringlnasally a vapor dosage unit of an admixture comprising 2-amino-6-methylheptane and a vasoconstrictor amine, such as for example, the preferred cyclohexyl 2-methylaminopropane in a ratio of from about 1:1 to about 9:1. The vapor dosage unit will be from about 0.25 mg. to about 1.5 mg. of total amine. Preferably the daily dose will be from about 0.25 mg. to about 12.0 mg.

of total amine.

Preferably the mixture will be present in the ratio of from about 1:1 to about 9:1 of the 2-amino-6-methylheptane to the 1-cyclohexyl-2-methylaminopropane.

The composition in addition to the essential active in gredients above, will desirably, though not necessarily, include an ingredient which will reduce the vapor pressure of the volatile amines, i.e., have a dampening elfect upon the amines and which will also desirably be of such a character as to have a soothing-nonirritating effect upon the tissues of the respiratory tract. By way of illustra tion, for example, this ingredient may be an alcohol, such as phenylethyl alcohol, benzyl alcohol, glycols such as propylene glycol, essential oils, as, for example, oil of lavender, oil of peppermint or the like or other substances which will have the indicated dampening effect.

A further means to produce a dampenng effect of the volatile amines present in this invention is to prepare a carbon dioxide addition product. This may be accomplished by the treatment of the amine with carbon dioxide in the absence or presence of water and may result in a carbamate or a carbonate or a mixture of the two.

If desired, in order that the composition may have a plesant fiavor, for example, oil of lavender, menthol or a mixture of these ingredients may be added. Other flavoring agents suitable for the compositions may also be added.

Further, the composition, when necessary, may contain an inert liquid vehicle, such as for example, dibutyl phthalate or benzyl salicylate or other comparable inert liquid vehicles.

The preferred aspect of this invention is the admixture of the 2-amino-6-methylheptane and l-cyclo-hexyl-Z- methylaminopropane in a ratio of approximately 2:1 combined with dibutyl phthalate, phenylethyl alcohol and a mixture of oils of lavender and menthol for flavoring.

The compositions in accordance with this invention which, as has been indicated, are for administration by nasal inhalation, may be prepared for use conveniently by charging into an inhaler adapted for inhalation nasally. The following examples are not limiting but are only illustrative of the compositions of this invention. The ingredients may be varied to obtain various dosages from the inhaler. The effective vapor dose emanating from the inhaler may vary from about .25 mg. to about 1.5 mg.

1 Oil of lavender and menthol in a 6:1 ratio.

The 2-amino-6-methylheptane and phenylethyl alcohol are mixed together and while mixing the distilled aromatics, dibutyl phthalate and 1-cyclohexyl-Z-methyl-aminopropane are added. When completely mixed 1.25 ml. of the above inhaler solution is pipetted to the end of a cotton pledget having a diameter of A5" and a length of 1%" present in the nose piece of the inhaler. The nose piece is immediately placed into the body of the inhaler and the inhaler capped tightly to avoid volatilization.

Insert inhaler into nostril and with other nostril closed, inhale twice. Repeat in other nostril. This method is repeated from one to eight times daily.

Example 2 Percent v./v. Ingredients of Inhaler Mg/Inhalcr Solution 2-amino-6-methylheptane 19. 48 150 Phenylethyl alcohol 30. 195 304 Distilled aromatics 30. 195 268 Dibutyl phthalate 20. 13 205 1 Oil of lavender and menthol in a 6:1 ratio.

Example 3 Percent v./v.

Ingredients of Inhaler Mg./Inhaler Solution Z-amino-G-methylheptsue 23. 53 250. 0 2-aminehcptane 15. 58 150. 0 Distilled aromatics 19. 79 220. 0 Phcnylethyl alcohol 19. 79 251. 9 Dibutyl phthalate 21. 31 278. 8

1 Oil of lavender and menthol in a 6:1 ratio.

The 2-amino-6-methylheptane and phenylethyl alcohol are mixed together and while mixing the distilled aromatics, dibutyl phthalate and Z-aminoheptane are t added. When completely mixed 1.25 ml. of the above inhaler solution is pipetted to the end of a cotton pledget having a diameter of and a length of 1%" present in the nose piece of the inhaler. The nose piece is immediately placed into the body of the inhaler and the inhaler capped tightly to avoid volatilization.

Insert inhaler into nostril and with other nostril closed, inhale twice. Repeat in other nostril. This method is repeated from one to eight times daily.

What is claimed is:

1. The method of relieving cough associated with upper respiratory tract irritation which comprises the nasal administration of a vapor dosage unit of from about 0.25 mg. to about 1.50 mg. of 2-amino-6-methylheptane.

2. The method of relieving cough associated with upper respiratory tract irritation which comprises the nasal administration of a daily dosage regimen of from about 0.25 mg. to about 12.0 mg. of 2-amino-6-methylheptane.

3. The method of relieving cough associated with upper respiratory tract irritation and concurrently relieving nasal congestion which comprises the nasal administration of a vapor dosage unit or" from about 0.25 mg. to about 1.5 mg. of an admixture comprising 2-amino-6- methylheptane and 1-cyclohexyl-2-methylaminopropane.

4. The method of relieving cough associated with upper respiratory tract irritation and concurrently relieving nasal congestion which comprises the nasal administration of a vapor dosage unit of from about 0.25 mg. to about 1.5 mg. of an admixture comprising 2-amino-6- methylheptane and 1 cyclohexyl-Z-methylaminopropane in a ratio of from about 1:1 to about 9:1.

5. The method of relieving cough associated with upper respiratory tract irritation and concurrently relieving nasal congestion which comprises the nasal administration of a daily dosage regimen of from about 0.25 mg. to about 12.0 mg. of an admixture comprising 2- amino-S-methylheptane and l-cyclohexyl-Z-methylaminopropane.

6. The method of relieving cough associated with upper respiratory tract irritation and concurrently relieving nasal congestion which comprises the nasal administration of a daily dosage regimen of from about 0.25 mg. to about 12.0 mg. of an admixture comprising 2- amino--methylhcptane and 1-cyclohexyl-Z-methy1aminopropane in a ratio of from about 1:1 to about 9:1.

7. A medicinal composition for the relief of cough associated with upper respiratory tract irritation and concurrent relief of nasal congestion comprising the volatile amines 2-arnino-6-methylheptane and 1- cyclohexyl -2- methylaminopropane.

8. A medicinal composition for the relief of cough associated with upper respiratory tract irritation and concurrent relief of nasal congestion comprising the volatile amines 2-amino-6-methylheptane and 1 cyclohexyl 2 methylaminopropane in a ratio of from about 1:1 to about 9:1.

9. A medicinal composition in accordance with claim 8 in that said composition is combined with an inert liquid vehicle.

References Cited in the file of this patent Rohrmann: J.A.C.S., vol 66, pp. 1516-1520, 1944. 

1. THE METHOD OF RELIEVING COUGH ASSOCIATED WITH UPPER RESPIRATORY TRACT IRRITATION WHICH COMPRISES THE NASSAL ADMINISTRATION OF A VAPOR DOSAGE UNIT OF FROM ABOUT 0.25 MG. TO ABOUT 1.50 MG. OF 2-AMINO-6-METHYLHEPTANE. 